RANKL is a member of the tumor necrosis factor (TNF) cytokine family which is a ligand for osteoprotegerin and functions as a key factor for osteoclast differentiation and activation. There are three isoforms of RANKL. Human RANKL is a soluble 20 kDa polypeptide, comprising the TNF homologous region of RANKL (176 amino acid residues). This protein was shown to be a dentritic cell survival factor and is involved in the regulation of T cell dependent immune response. T cell activation was reported to induce expression of this gene and lead to an increase of osteoclastogenesis and bone loss. This protein was shown to activate antiapoptotic kinase AKT/PKB through a signaling complex involving SRC kinase and tumor necrosis factor receptor associated factor (TRAF) 6, which indicated that this protein may have a role in the regulation of cell apoptosis. RANKL deficient mice show severe osteoporesis and complete absence of osteoclasts as a result of lack of osteogenesis.

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